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Genetic association of recovery from eating disorders: The role of gaba receptor snps

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Overview

authors

  • Bloss, C. S.
  • Berrettini, W.
  • Bergen, A. W.
  • Magistretti, P.
  • Duvvuri, V.
  • Strober, M.
  • Brandt, H.
  • Crawford, S.
  • Crow, S.
  • Fichter, M. M.
  • Halmi, K. A.
  • Johnson, C.
  • Kaplan, A. S.
  • Keel, P.
  • Klump, K. L.
  • Mitchell, J.
  • Treasure, J.
  • Woodside, D. B.
  • Marzola, E.
  • Schork, Nicholas
  • Kaye, W. H.

publication date

  • 2011

journal

  • Neuropsychopharmacology  Journal

abstract

  • Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, 'ill') or absence (n=115 no symptoms in the past year, ie, 'recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10(-6), false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10(-6), FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (γ-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients.

subject areas

  • Adult
  • Cohort Studies
  • Feeding and Eating Disorders
  • Female
  • Follow-Up Studies
  • Genetic Association Studies
  • Humans
  • Polymorphism, Single Nucleotide
  • Receptors, GABA
  • Receptors, GABA-A
  • Recovery of Function
  • Young Adult
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Identity

PubMed Central ID

  • PMC3176559

International Standard Serial Number (ISSN)

  • 0893-133X

Digital Object Identifier (DOI)

  • 10.1038/npp.2011.108

PubMed ID

  • 21750581
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Additional Document Info

start page

  • 2222

end page

  • 2232

volume

  • 36

issue

  • 11

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